Recent reports have identified a specific oncogenic mutation L265P of the MYD88 gene in approximately 90% of the patients with Waldenström's macroglobulinemia. MYD88 is a key linker protein in the signaling pathway of Toll Like Receptors (TLRs) 7, 8, and 9, and IMO-8400 is an oligonucleotide specifically designed to inhibit TLRs 7,8, and 9. The scientific hypothesis for use of IMO-8400 to treat patients with Waldenström's macroglobulinemia depends on the inhibition of mutant MYD88 signaling in the TLR pathway, thereby interrupting the proliferation of cell populations responsible for the propagation of the disease.
Name: IMO-8400
Type: DrugIMO-8400 at escalating dose levels
Description: Assessment of adverse events, injection site reactions and concomitant medications in escalating dose levels of IMO-8400.
Measure: Safety and tolerability of IMO-8400 in patients with Waldenstrom's Macroglobulinemia Time: Duration of studyDescription: To assess the treatment effect (clinical activity) of escalating dose levels of IMO-8400 using disease-specific international guidelines for classifying clinical response.
Measure: Assess the treatment effect Time: Duration of studyDescription: To identify an appropriate dose of IMO-8400 for further clinical evaluation.
Measure: Identify an appropriate dose of IMO-8400 Time: Duration of studyDescription: To characterize the pharmacokinetics of escalating dose levels of IMO-8400 administered once weekly by SC injection.
Measure: Characterize PK Time: Duration of studySingle Group Assignment
There is one SNP
Phase 1/2 Dose Escalation Study in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia Recent reports have identified a specific oncogenic mutation L265P of the MYD88 gene in approximately 90% of the patients with Waldenström's macroglobulinemia. --- L265P ---